Longer duration of antiretroviral therapy correlated with a return from low to normal "good" high-density lipoprotein cholesterol (HDL-C) in a 2900-person French study [1]. Longer use of protease inhibitors (PIs), nonnucleosides (NNRTIs), nucleosides, and integrase inhibitors all boosted chances of regaining a normal HDL-C level, as did several markers of good antiretroviral response.

People with HIV infection run a higher risk of subnormal HDL-C levels, but the factors influencing a return to normal HDL have not been well studied. French clinicians addressed that question in a study of 2905 people whose HDL-C was measured periodically after a 12-hour fast. The researchers defined low HDL-C as a level below 0.9 mmol/L (35 mg/dL).

Through an average follow-up of 3.72 years, the investigators measured HDL-C 29,263 times. Cohort members had a median of 8 HDL-C measures. Age at inclusion in the cohort averaged 41.5 years, and 2002 cohort member (69%) were men. Most cohort members, 2507 (86%) had a CD4 count above 200 when they entered the group. HIV infection duration at the end of follow-up averaged 11.7 years. Among antiretroviral-treated people, 61% had taken a PI and 40% an NNRTI.

There were 1454 people with no low HDL-C levels during follow-up, 1324 with at least one low HDL-C, and 127 who always had a low HDL-C. Half of these people, then, had subnormal HDL-C at some point in 3.7 years of follow-up.

Statistical analysis considering antiretroviral classes and adjusted for number of HDL-C measurements and treatment with lipid-lowering drugs identified several independent predictors of transition from low to normal HDL-C at the following hazard ratios (HR) and 95% confidence intervals (CI):

The researchers concluded that female gender and low triglycerides, glucose, and low-density lipoprotein all favor a return to normal HDL-C levels. But they proposed that variables related to control of HIV infection (particularly treatment with PIs, NNRTIs, and raltegravir) are the main drivers HDL-C normalization. They suggested that the association between a higher CD4/CD8 ratio and return to a normal HDL-C reflects quelling of the inflammatory state induced by poorly controlled HIV infection.